Chromatin modifying activities for construction of appropriate epigenetic landscapes by polycomb repressive complex 2 (PRC2) play an essential role in development and tumorigenesis. However, the spatiotemporal mechanisms by which PRC2 achieves diverse epigenomes for specific tissue or cellular contexts remain poorly understood. Here, we discovered that LATS2 knockout causes dysregulation of PRC2 and subsequent transcriptome changes for differentiation in both mouse and human cells. LATS2 depletion dependent dysregulation of PRC2 also effects H3K4me3 and forms negative feedback loop for maintenance of PRC2. Further analyses reveal that LATS2 on chromatin binds to EZH2 and LATS2 has ability to phosphorylate PRC2 in vitro. These LATS2 dependent H3K27me3 targets are highly induced during neurogenesis, and statistical analysis of glioblastoma multiforme reveals that LATS2-high cases show more dedifferentiated transcriptome and poor prognosis with silencing of H3K27me3 targets. These observations suggest that LATS2-mediated epigenome coordination is pivotal for development and disease, including cancer. Overall design: mRNA of LATS2 KO HeLa-S3 cells rescued by empty vector, wild-type LATS2 or kinase-dead LATS2 were subjected to deep sequencing profiling using Illumina HiSeq 2500
LATS2 Positively Regulates Polycomb Repressive Complex 2.
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View SamplesWe identify sites of combinatorial control by performing high throughput ChIP experiments on p300, CREB-binding protein (CBP), the deacetylase SIRT1 and on multiple DNA-binding transcription factors in three different tissues. We present a quantitative model of transcriptional regulation that reveals the contribution of each binding site to tissue-specific gene expression in several mouse cell types. Binding to both evolutionarily conserved and non-conserved sequences is found to contribute significantly to transcriptional regulation. We demonstrate that binding location strongly predicts the expression level of nearby genes.
A quantitative model of transcriptional regulation reveals the influence of binding location on expression.
Specimen part
View SamplesCellular dedifferentiation signifies the withdrawal of cells from a specific differentiated state into a stem cell-like undifferentiated state. However, the mechanism of dedifferentiation remains obscure. We showed that follicular granulosa cells (GC), which have distinct functions in vivo, can dedifferentiate during culture in vitro and acquire multipotency.
Dedifferentiated follicular granulosa cells derived from pig ovary can transdifferentiate into osteoblasts.
Specimen part
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Heme ameliorates dextran sodium sulfate-induced colitis through providing intestinal macrophages with noninflammatory profiles.
Specimen part, Treatment
View SamplesIn murine large intestinal lamina propria, CX3CR1high resident Mfs possess anti-inflammatory properties and thereby support intestinal homeostasis. Unlike other tissue-resident Ms, transcription factors that regulate differentiation and function of CX3CR1high Ms in the large intestine are poorly understood. Thus, to identify transcription factors specifically expressed in CX3CR1high Ms among large intestinal lamina propria innate myeloid cells, we comprehensively analyzed the genes expression profiles in CX3CR1high Ms, CX3CR1- CD11b+ CD11c+ cells, CD11b- CD11chigh DCs, and CD11b+CD11c- cells.
Heme ameliorates dextran sodium sulfate-induced colitis through providing intestinal macrophages with noninflammatory profiles.
Specimen part
View SamplesTo determine the functions of Spi-C in innate immune responses, we investigated the overall gene expression patterns in M-CSF-BMDMFs prepared from Spicflox/flox and Lyz2-cre; Spicflox/flox mice. M-CSF-BMDMFs were stimulated with or without LPS following heme treatment and used for RNA-seq analysis. Overall design: Control and Spic–/– BMDMF pretreated with 40 µM hemin for 18 h were stimulated with (designated 'CNT_4' and 'cKO_4', respectively) or without (designated 'CNT_0' and 'cKO_0', respectively) 100 ng/ml LPS for 4 h.
Heme ameliorates dextran sodium sulfate-induced colitis through providing intestinal macrophages with noninflammatory profiles.
Specimen part, Treatment, Subject
View SamplesInnate immune cells control acute eosinophilic lung inflammation induced by cystein proteases. Here we characterize the dynamic change of gene expression profile in basophils, natural helper cells and eosinophils during lung inflammation via cystein protease Overall design: Examination of mRNA levels in individual cell populations, basophils, natural helper cells and eosinophils of the lung from naïve mice and papain treated mice.
Basophil-derived interleukin-4 controls the function of natural helper cells, a member of ILC2s, in lung inflammation.
No sample metadata fields
View SamplesTo identify the “time-lapse” TF networks during B lineage commitment, we established multipotent progenitors harboring a tamoxifen-inducible form of Id3, an in vitro system where virtually all cells became B cells within 6 days by simply withdrawing 4-OHT. In this study, transcriptome analysis at multiple time points was performed using the culture system. Overall design: Time-course transcriptomic profiles of multipotent iLS cells toward B committed cells were analyzed by deep sequencing, basically in triplicate, using Illumina Hiseq platform.
Three-step transcriptional priming that drives the commitment of multipotent progenitors toward B cells.
Specimen part, Cell line, Subject, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
MAFG is a transcriptional repressor of bile acid synthesis and metabolism.
Treatment
View SamplesSpecific bile acids are potent signaling molecules that modulate metabolic pathways affecting lipid, glucose and bile acid homeostasis, and the microbiota. Bile acids are synthesized from cholesterol in the liver, and the key enzymes involved in bile acid synthesis (Cyp7a1, Cyp8b1) are regulated transcriptionally by the nuclear receptor FXR. We have identified an FXR-regulated pathway upstream of a transcriptional repressor that controls multiple bile acid metabolism genes. We identify MafG as an FXR target gene and show that hepatic MAFG overexpression represses genes of the bile acid synthetic pathway and modifies the biliary bile acid composition. In contrast, loss-of-function studies using MafG(+/-) mice causes de-repression of the same genes with concordant changes in biliary bile acid levels. Finally, we identify functional MafG response elements in bile acid metabolism genes using ChIP-seq analysis. Our studies identify a molecular mechanism for the complex feedback regulation of bile acid synthesis controlled by FXR
MAFG is a transcriptional repressor of bile acid synthesis and metabolism.
Treatment
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